crossing96/oncoscreening huggingface dataset:
Salvage cystectomy after failure of interstitial radiotherapy and external beam radiotherapy for bladder cancer.	OBJECTIVE: To evaluate the long-term results of salvage cystectomy after interstitial radiotherapy (IRT) and external beam radiotherapy (EBRT) for transitional cell carcinoma, and to assess the morbidity and functional results of the different urinary diversions used. PATIENTS AND METHODS: The records of 27 patients treated with salvage cystectomy in one institution between 1988 and 2003 were retrospectively analysed. RESULTS: Salvage cystectomy was used after failure of IRT in 14 or EBRT in 13 patients, with a 3- and 5-year survival probability of 46% (95% confidence interval 26-65) and 33 (11-54)%. The 5-year overall survival after cystectomy was 54% after IRT and 14% after EBRT (P = 0.12). Tumour category, response to radiation, American Society of Anesthesiology score, and complete tumour resection had a significant influence on survival. Five of seven patients with incomplete resection died because of local disease, with a median survival of 5 months. There was clinical understaging after radiotherapy in 41% of patients. Nine patients had an orthotopic neobladder, with complete day- and night-time continence in eight and four, respectively. All patients but one had good voiding function. There were early complications in two and late complications in six patients (for Bricker, seven of 14 and none; for Indiana, none of four and two of four). The duration of hospitalization was not influenced by the type of diversion. Erectile function was maintained in four of six patients after a sexuality-preserving cystectomy and neobladder. CONCLUSIONS: Salvage cystectomy can be performed with acceptable morbidity using any type of urinary diversion. Understaging after radiotherapy is common, but preoperative selection needs improving. A very significant factor for an adverse outcome and death from local tumour recurrence was incomplete resection, suggesting that salvage cystectomy should only be attempted if complete resection is probable.	bladder
A multi-institutional phase II trial of gemcitabine plus paclitaxel in patients with locally advanced or metastatic urothelial cancer.	The purpose of the study was to evaluate response and survival in patients with metastatic urothelial cancer treated with combination gemcitabine and paclitaxel administered on a biweekly schedule at doses of 3000 mg/m2 and 150 mg/m2, respectively. Patients with adequate organ function and performance status were accrued through 7 institutions, stratified by prior therapy status, and treated as noted. Response was evaluated by 1979 bi-dimensional World Health Organization (WHO) criteria. Of 55 eligible patients, 17 had a partial and 5 had a complete response rate for an overall response rate of 40% (27-54%). One complete response and one partial response were observed in the 6 previously treated patients. Overall median survival was 11.8 months (11.9 months in the chemonaive cohort). Grade 3 or 4 myelosuppression occurred in 56%, but only 4 serious infections were observed. We conclude that because of a lower than expected complete response rate, even when corrected for prognostic groupings, this regimen is not recommended for routine use in patients with metastatic urothelial cancer. Insufficient patients with poor renal function or prior therapy were accrued to reach conclusions regarding its utility in these subgroups.	bladder
Quantitative microscopy of human DNA topoisomerase II-alpha expression in transitional cell carcinoma of the bladder.	OBJECTIVE: To compare the nuclear size of various grades of transitional cell carcinoma (TCC) stained immunohistochemically with the nuclear enzyme topoisomerase II-alpha (topo II-alpha) in bladder urothelial neoplasms. STUDY DESIGN: Histologic sections from 53 consecutive papillary bladder neoplasms were stained immunohistochemically for topo II-alpha expression. There were 18 (33.9%) urothelial neoplasms of low malignant potential (UNLMP), 18 (33.9%) low grade urothelial carcinoma (LGUCa), and 17 (32%) with high grade urothelial carcinoma (HGUCa). The histologic slides were photographed at 400 x magnification and then projected on a screen, and the area with stained nuclei was measured. RESULTS: The cells and nuclei in HGUCa were significantly larger than in LGUCa (P < .05) and UNLMP (P < .01). CONCLUSION: Calculation of the area fraction of nuclei in TCC of the bladder stained with topo II-alpha is an additional method of establishing the grade of these tumors.	bladder
Occupation and bladder cancer risk in a population-based case-control study in New Hampshire.	OBJECTIVE: To identify occupations with excess bladder cancer risk in New Hampshire, where bladder cancer mortality rates have been elevated for decades. METHODS: Lifetime occupational histories were obtained from interviews with 424 cases and 645 controls in a population-based case-control study. Unconditional logistic regression models were used to estimate odds ratios (Ors) and 95% confidence intervals (CI) for each occupation, adjusted for age and smoking. Analyses by duration of employment were carried out and interactions with smoking were examined. RESULTS: Male tractor-trailer truck drivers had an elevated risk for bladder cancer (OR = 2.4, CI = 1.4-4.1), with a significant positive trend in risk with increasing duration of employment (P (trend) = 0.0003). Male metal/plastic processing machine operators also had a significant excess (OR = 4.9, CI = 1.6-15.1), attributable mainly to molding/casting machine operators (OR = 16.6, CI = 2.1-131). Elevated risk was also observed for male fabricators, assemblers, and hand workers (OR = 1.8, CI = 1.0-3.4). Women in certain sales occupations (sales clerks, counter clerks, and cashiers) had a significant excess risk (OR = 2.2, CI = 1.3-3.9) and a significant trend with duration of employment (P (trend) = 0.016), as did female health service workers (OR = 4.1, CI = 1.6-10.7; P (trend) = 0.014). There was a positive interaction between smoking and employment as a health service worker (p = 0.036). CONCLUSIONS: These findings are generally consistent with previous studies. Elevated risks for male molding/casting machine operators, female salesworkers, and female health service workers, especially those with a history of smoking, require further investigation.	bladder
Specific chromosome aberrations in peripheral blood lymphocytes are associated with risk of bladder cancer.	Specific chromosome aberrations in peripheral blood lymphocytes (PBLs) in chromosomes 9 and 11 may be associated with bladder cancer. To investigate this hypothesis, in this study, we used a whole-chromosome painting technique to detect chromosomal aberrations in PBLs from 100 patients with bladder cancer and 100 matched controls. We also used a locus-specific fluorescence in situ hybridization technique to study 9p21 and cyclin D1 gene (CCND1) aberrations in PBLs of 10 patients and 10 controls and in tumor tissues of 38 additional cases. The chromosome-painting analysis showed that there were more aberrations of chromosomes 9 and 11 in bladder cancer patients than in controls. When categorized by type, the number of deletions of 9p and of translocations of chromosome 11 was significantly higher in patients than in controls (P < 0.05). Stratified analysis showed a larger odds ratio (OR) for bladder cancer in individuals with either a 9p deletion or a chromosome 11 translocation/amplification and an even larger OR in individuals with both aberrations. Using locus-specific analysis, we found that 9p21 aberrations occurred more frequently in bladder cancer patients (12.1 per 1,000 interphase cells) than in controls (6.4 per 1,000 interphase cells, P < 0.05); CCND1 translocation and amplification were observed only in bladder cancer patients. Tumor tissue analysis showed that aberrations of 9p21 (40.0 per 100 interphase cells) and CCND1 (43.8 per 100 interphase cells) were very common. Thus, we concluded that 9p deletions and translocations of chromosome 11, especially at 9p21 and CCND1, are associated with bladder cancer.	bladder
[Bladder villous adenoma: report of a new case].	OBJECTIVES: Villous adenoma is a benign neoplasia, the appearance of which in the urinary tract is extraordinarily unfrequent. We report a new case recently experienced in our department. METHODS: We report the case with its past urologic history, clinical picture, diagnostic tests, and treatment. RESULTS: Pathologic report confirmed the diagnosis of bladder villous adenoma, being transurethral resection the only treatment applied to leave the patient disease-free. CONCLUSIONS: Prognosis of this kind of neoplasia, which is unfrequent, is excellent; being endoscopic resection curative, with no local or distant progression, except in cases associated with adenocarcinoma foci, in which local recurrence or distant metastasis are possible, and a more aggressive treatment might be indicated.	bladder
Assessing the need to update prevention guidelines: a comparison of two methods.	BACKGROUND: An important concern for developers of clinical practice guidelines is how best to determine when guidelines require updating to ensure they remain current and evidence based. Because of the high costs associated with updating guidelines, recent attention has focused on approaches that can reliably assess the extent of updating required. Recently, Shekelle and colleagues proposed a model of limited literature searches with modest expert involvement as a way to reduce the cost and time requirements for assessing whether a guideline needs updating. METHODS: The main objective of this study was to compare the Shekelle et al. assessment model (review approach) and a conventional process using typical systematic review methods (traditional approach) in terms of comprehensiveness and effort. We modeled the review approach on that by Shekelle and colleagues but refined it iteratively over three phases to achieve greater efficiency. Using both methods independently, we assessed the need to update six topics from the 1996 Guide to Clinical Preventive Services from the US Preventive Services Task Force. Main outcomes included completeness of study identification, importance of missed studies and the effort involved. RESULTS: Although the review approach identified fewer eligible studies than the traditional approach, none of the studies missed was rated as important by task force members acting as liaisons to the project with respect to whether the topic required an update. On average, the review approach produced substantially fewer citations to review than the traditional approach. The effort involved and potential time saving depended largely on the scope of the topic. CONCLUSIONS: The revised review approach provides an efficient and acceptable method for judging whether a guideline requires updating.	bladder
A functional polymorphism in RGS6 modulates the risk of bladder cancer.	RGS proteins negatively regulate heterotrimeric G protein signaling. Recent reports have shown that RGS proteins modulate neuronal, cardiovascular, and lymphocytic activity, yet their role in carcinogenesis has not been explored. In an epidemiologic study of 477 bladder cancer patients and 446 matched controls, three noncoding single-nucleotide polymorphisms (SNPs) in RGS2 and RGS6 were each associated with a statistically significant reduction in bladder cancer risk. The risk of bladder cancer was reduced by 74% in those individuals with the variant genotype at all three SNPs (odds ratio, 0.26; 95% confidence interval, 0.09-0.71). When the SNPs were analyzed separately, the RGS6-rs2074647 (C-->T) polymorphism conferred the greatest overall reduction in risk of bladder cancer (odds ratio, 0.66; 95% confidence interval, 0.46-0.95). These reductions in risk were more pronounced in ever smokers, suggesting a gene-environment interaction. In transfection assays, the RGS6-rs2074647 (C-->T) polymorphism increased the activity of a luciferase-RGS fusion protein by 2.9-fold, suggesting that this SNP is functionally significant. Finally, we demonstrate that RGS2 transcripts and several splice variants of RGS6 are expressed in bladder cancer cells. These data provide the first evidence that RGS proteins may be important modulators of cancer risk and validate RGS6 as a target for further study.	bladder
Autocrine over expression of fibronectin by human transitional carcinoma cells impairs bacillus Calmette-Guerin adherence and signaling.	PURPOSE: Bacillus Calmette-Guerin (BCG) binds to the tumor cell as a result of mycobacterial receptors for fibronectin (FN). Cell surface bound FN serves as a bridge through which BCG attaches to the tumor cell. Despite the importance of FN studies have demonstrated an idiosyncratic decrease in BCG adherence in response to exogenous FN. We evaluated the effect of exogenous and autocrine FN on the ability of BCG to adhere to the tumor cell surface and initiate cellular signaling. MATERIALS AND METHODS: BCG adherence to parental 253J and FN over expressing 253JTGFbeta1-8 cells as well as to the intrinsic FN expressing cell line 647V was quantified using green fluorescent protein-BCG. Experiments were performed to assess the effect of FN on BCG initiated signal transduction through nuclear factor kappaB and AP1. Finally, the integrity of the BCG activated signaling pathway in transforming growth factor-beta1/FN over expressors was assessed using antibody mediated cross-linking of the FN receptor. RESULTS: BCG adherence was decreased in cell lines with high autocrine expression of FN. Exogenous FN prevented BCG induced transactivation of nuclear factor kappaB and AP1 reporter constructs. No BCG stimulated signaling to these reporters could be detected in FN over expressing 253J cells. NonFN dependent alpha5beta1 cross-linking initiated signal transduction in FN over expressing cells. CONCLUSIONS: We propose that by saturating cellular and BCG receptors excess FN expression decreases the ability of cellular or mycobacterial bound FN to bind vacant receptors on BCG or on the cell. Excess FN inhibits BCG adherence and BCG initiated signal transduction.	bladder
Mechanisms of bacillus Calmette-Guerin mediated natural killer cell activation.	PURPOSE: Natural killer (NK) cells are of crucial importance for bacillus Calmette-Guerin (BCG) mediated antitumor effects. We defined the mechanisms of BCG mediated NK cell activation in vitro. MATERIALS AND METHODS: A standard Cr release assay was used to measure the cytotoxicity of BCG activated NK cells. Using the MACS system (Miltenyi Biotec, Bergisch-Gladbach, Germany) we depleted various immune cell subpopulations from BCG stimulated peripheral blood mononuclear cells to phenotype activated NK cells. During the stimulation process anticytokine antibodies and recombinant cytokines were added to define their role in NK cell activation. For costimulation studies peripheral blood mononuclear cells were separated into lymphocytes and monocytes by counterflow-centrifugation (elutriation). Inhibitory NK cell receptor expression on activated NK cells was measured by flow cytometry by antiCD3, antiCD56 and anti-inhibitory NK cell receptor triple staining. RESULTS: The accessory function of monocytes was indispensable for BCG mediated NK cell activation. However, the stimulatory potential of monocytes did not require direct cell-cell contact to NK cells or major histocompatibility complex dependent antigen presentation to T cells. Monocyte derived interleukin (IL)-12 and to a lesser extent interferon (IFN)-alpha were key mediators for stimulating BCG induced NK cell cytotoxicity and IFN-gamma production. In contrast, IL-10 inhibited NK cell cytotoxicity and IL-18 did not show any effect. Exogenous recombinant IFN-alpha and IL-12 enhanced BCG mediated secretion of IFN-gamma and yet BCG induced NK cell cytotoxicity remained unchanged. While the CD158a and CD158b subsets did not have a significant role, NKG2A cells represented the predominant cytolytic subset in BCG activated NK cells. CONCLUSIONS: Following BCG stimulation the monocyte derived TH1 cytokines IL-12 and IFN-alpha activate tumor cytotoxic CD3/CD56/NKG2A NK cells. Our results elucidate NK activating mechanisms that are operative during BCG immunotherapy for bladder cancer and are relevant for an early, innate antimycobacterial immune response.	bladder
Synergistic inhibition of tumor growth and metastasis by combined treatment with TNP-470 and gemcitabine in a human bladder cancer KoTCC-1 model.	PURPOSE: TNP-470 (O-(chloroacetylcarbamoyl)fumagillol) is a potent inhibitor of angiogenesis that was reported to enhance synergistically the antitumor effects of cytotoxic agents. We evaluated the effectiveness of combined treatment with TNP-470 and gemcitabine in vitro and in vivo using highly metastatic human bladder cancer KoTCC-1 cells. MATERIALS AND METHODS: The in vitro growth inhibitory and apoptotic effects of gemcitabine and/or TNP-470 on KoTCC-1 cells were assessed using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and TUNEL staining, respectively. We then evaluated the combined effect of gemcitabine and TNP-470 therapy after subcutaneous and orthotopic injection of KoTCC-1 cells into athymic nude mice. Established tumors were analyzed by TUNEL staining and immunohistochemical staining of CD31 to quantify microvessel density. RESULTS: In vitro TNP-470 enhanced the cytotoxic effect of gemcitabine on KoTCC-1 cells, decreasing its IC50 by more than 50%. This combined treatment significantly induced apoptosis compared with treatment with either agent alone. In vivo combined treatment with TNP-470 and gemcitabine significantly decreased tumor growth after subcutaneous and orthotopic injection into athymic nude mice and significantly decreased the incidence of lymph node metastasis after arthotopic injection compared with either agent alone. Immunohistochemical analysis of the subcutaneous tumor after each treatment demonstrated that gemcitabine administration significantly induced apoptotic cell death. In contrast, a significant decrease in microvessel density was observed after TNP-470 treatment. CONCLUSIONS: These findings demonstrate that TNP-470 and gemcitabine act synergistically to inhibit tumor growth and metastasis by enhancing apoptosis and suppressing angiogenesis.	bladder
Attempted nerve sparing surgery and age have a significant effect on urinary continence and erectile function after radical cystoprostatectomy and ileal orthotopic bladder substitution.	PURPOSE: We assessed factors influencing urinary continence and erectile function after radical cystoprostatectomy and ileal orthotopic bladder substitution. MATERIALS AND METHODS: Of 381 consecutive men undergoing radical cystoprostatectomy and ileal orthotopic bladder substitution between April 1985 and June 2003, 331 (87%) met the inclusion criteria and were enrolled in the analysis. Kaplan-Meier models and multivariate analysis applying Cox regression were used to evaluate factors influencing postoperative urinary continence and erectile function. RESULTS: In univariate analysis, attempted nerve sparing and age younger than 65 years were significantly associated with better daytime (p = 0.002 and p = 0.007, respectively) and nighttime continence (p = 0.036 and p = 0.005, respectively). In multivariate analysis the rate of daytime continence was significantly higher in patients with attempted nerve sparing (hazards ratio [HR] 1.4, 95% confidence interval [CI] 1.05-1.87) and nighttime continence was significantly better in patients younger than 65 years (HR 1.39, 95% CI 1.07-1.8). Daytime continence was significantly better (p <0.0001) and was achieved more quickly than nighttime continence (p <0.0001). The time to achieve daytime continence was shorter for patients with attempted nerve sparing (p = 0.012). In multivariate analysis erectile function recovered significantly more often in patients with attempted nerve sparing (HR 2.59, 95% CI 1.24-5.39) and in those younger than 65 years (HR 2.98, 95% CI 1.83-4.85). CONCLUSIONS: After radical cystoprostatectomy and ileal orthotopic bladder substitution, attempted nerve sparing and age younger than 65 years are associated with improved urinary continence. Attempted nerve sparing has the greatest impact on daytime continence and age has the greatest impact on nighttime continence. Attempted nerve sparing and younger age are both associated with more frequent recovery of erectile function.	bladder
Hand assisted laparoscopic cystectomy with minilaparotomy ileal conduit: series report and comparison with open cystectomy.	PURPOSE: To achieve less patient morbidity our initial experience with hand assisted laparoscopic (HAL) cystectomy was compared with our results of open cystectomy with similar urinary diversion. MATERIALS AND METHODS: During 18 months 36 cystectomies were performed, including 20 with open continent diversion. A prospective, nonrandomized comparison of the remaining 16 consecutive cystectomies with ileal conduit diversion (hand assisted laparoscopic cystectomy and open cystectomy in 8 cases each) was performed. Of the 16 cystectomies 13 were performed for muscle invasive bladder cancer. Standard parameters were compared concerning patient operative and postoperative courses using statistical analysis with the 2-tailed t test. A novel surgical technique for completing these HAL procedures is described and compared to standard open cystectomy and ileal conduit diversion. RESULTS: A total of 16 patients successfully underwent open (8) and HAL (8) cystectomy with an ileal conduit. Mean estimated blood loss in the HAL and open groups was 637 and 957 cc, respectively (p = 0.23). The mean postoperative parenteral analgesia administered was 31 mg in the HAL group vs 149 mg in the open group (p = 0.01). The HAL and open groups had a mean length of stay of 6.4 vs 9.8 days (p = 0.06). Mean operative time did not differ significantly between the HAL and open groups (403 and 420 minutes, respectively). Regular diet was resumed at 4.5 days in the HAL group vs 7.9 days in the open group (p = 0.05). Hospital length of stay was 6.4 vs 9 days for HAL vs open cases (p = 0.06). CONCLUSIONS: To our knowledge this represents the first reported series of patients undergoing HAL cystectomy with urinary diversion. HAL cystectomy with an ileal conduit appears to have less estimated blood loss and postoperative analgesic requirements, shorter length of stay and earlier return of bowel function than open cystectomy. Oncological efficacy was preserved in the short term.	bladder